Selank

Selank is a synthetic heptapeptide developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is a structural analogue of the immunomodulatory peptide tuftsin (Thr-Lys-Pro-Arg), extended with a C-terminal Pro-Gly-Pro sequence that confers resistance to enzymatic degradation. Selank was approved in Russia in 2009 as an anxiolytic and nootropic medication, marketed as a 0.15% nasal drop solution.

The peptide is notable for its dual anxiolytic-nootropic profile — it reduces anxiety without the sedation, cognitive impairment, or dependence potential associated with benzodiazepines. Its mechanism involves modulation of GABAergic neurotransmission and immune-related gene expression rather than direct GABA receptor binding, which accounts for its distinct side effect profile. Selank is structurally and pharmacologically related to Semax, another Russian-developed neuropeptide, though the two target different receptor systems and are sometimes used in combination.

Selank's anxiolytic effects are mediated primarily through modulation of GABAergic neurotransmission. Unlike benzodiazepines, which bind directly to the GABA-A receptor, Selank alters the expression of genes encoding GABA-A receptor subunits and enzymes involved in GABA synthesis and degradation. This indirect modulation produces anxiolysis without allosteric potentiation of GABA currents, which is why Selank lacks the sedation and tolerance development associated with benzodiazepine use.

The tuftsin-derived portion of the molecule confers immunomodulatory activity. Tuftsin is a natural tetrapeptide released by enzymatic cleavage of the Fc domain of IgG and is known to stimulate phagocytosis and modulate cytokine production. Selank retains this activity, modulating expression of interleukins, chemokines, and their receptors in brain tissue. This neuroimmune crosstalk may contribute to its cognitive effects, as neuroinflammation is increasingly recognized as a factor in cognitive decline. Selank also influences enkephalin metabolism by inhibiting enkephalin-degrading enzymes, which may contribute to its anxiolytic and mood-stabilizing properties through endogenous opioid system modulation.